The stimulus‐secretion coupling of amino acid‐induced insulin release: insulinotropic action of branched‐chain amino acids at physiological concentrations of glucose and glutamine

Abstract

The stimulant action of branched‐chain amino acids upon insulin release was examined in rat pancreatic islets incubated at physiological concentrations of D‐glucose and L‐glutamine. In the presence of the latter nutrients, L‐leucine and L‐isoleucine used together at a physiological concentration (0.25 mmol/1 each) doubled insulin secretion rate. The effect of L‐leucine upon insulin release was dose‐related without any indication of a threshold phenomenon. The insulinotropic action of L‐leucine was mimicked, to a limited extent, by its nonmetabolized analogue, 2‐aminobicyclo[2,2,l] heptane‐2‐carboxylic acid, l‐Glutamine slightly inhibited glucose‐stimulated insulin release. It is concluded that, under close‐to‐physiological conditions, L‐leucine stimulates insulin release by acting in the islet cells both as a fuel and as an allosteric activator of glutamate dehydrogenase.